TRANSNEURONAL SIGNALS FOR AFFERENT REGULATION

传入活动已被证明可以调节许多属性 突触后神经元。 众所周知，传入输入调节 突触后神经元的电活动通过 神经递质。 然而，传入输入也调节代谢 突触后神经元的活动，特别是在发育早期。 的 后一种形式的跨神经元调节的信号尚不清楚。 小鸡的脑干听觉系统已被证明是一个有用的 用于研究细胞代谢的跨神经元调节的系统。 大细胞核（NM，耳蜗）中的二级听觉神经元 核）从同侧听觉接收唯一的兴奋性输入 神经。 消除一侧听觉神经的活动 大脑已被证明可以改变 NM 神经元的许多特性。 对于 例如，几天后，NM 中的一部分神经元死亡，并且 其余尺寸缩小。 听神经消除后早期 幼鸡的活动，NM 神经元代谢的变化 观察到。 例如，1小时内，急剧下降 大脑同侧 NM 神经元合成蛋白质。 这样的 然而，未观察到 NM 神经元结构和功能的变化 消除成年鸟类的听觉神经活动后。 拟议的实验研究了参与调节的信号 NM 神经元的电活动和代谢活动。 这些实验将在幼年（1-2 周大）和 成年（1岁）鸡。 电活动的调节是 首先通过分析不同的解剖分布进行研究 兴奋性氨基酸受体的类别。 生理效应 然后通过应用特定的方法来评估兴奋性氨基酸 激动剂和拮抗剂，同时从 NM 神经元进行细胞内记录 体外脑切片制剂。 研究代谢调节 通过评估体外切片制备中蛋白质合成的变化 经过各种治疗后。 单侧刺激听神经 体外已被证明在蛋白质合成中产生类似的变化 那些在体内观察到的。 特定激动剂和拮抗剂的应用 将评估不同类型的兴奋性氨基酸的相对作用 大脑跨神经元调节中的受体和第二信使系统 干听觉系统，2）理解负责的信号 该系统中神经元代谢的调节以及3） 了解与年龄相关的差异，这可能是年龄的原因 神经元对传入神经改变的敏感性的依赖性 活动。

Afferent activity has been shown to regulate a number of properties of postsynaptic neurons. It is well known that afferent input regulates the electrical activity of postsynaptic neurons through the action of neurotransmitters. Afferent input, however, also regulates the metabolic activity of postsynaptic neurons, particularly early in development. The signals for this latter form of transneuronal regulation are not known. The brain stem auditory system of the chick has proven to be a useful system for investigation transneuronal regulation of cellular metabolism. Second-order auditory neurons in nucleus magnocellularis (NM, the cochlear nucleus) receive their sole excitatory input from the ipsilateral auditory nerve. Elimination of activity in the auditory nerve on one side of the brain has been shown to alter a number of properties of NM neurons. For example, after a couple of days, a portion of the neurons in NM die and the rest shrink in size. Early after the elimination of auditory nerve activity in young chicks, changes in metabolism in NM neurons have been observed. For example, within 1 hour, there is a dramatic decrease in protein synthesis by NM neurons on the ipsilateral side of the brain. Such changes in NM neurons structure and function, however, are not observed after elimination of auditory nerve activity in adult birds. The proposed experiments investigate the signals involved in the regulation of both the electrical activity and metabolic activity of NM neurons. These experiments will be carried out on both young (1-2 week old) and adult (1 year old) chickens. Regulation of electrical activity is investigated first by analyzing the anatomical distribution of different classes of excitatory amino acid receptors. The physiological effects of excitatory amino acids are then assessed by application of specific agonists and antagonists while recording intracellularly from NM neurons in an in vitro brain slice preparation. Metabolic regulation is investigated by assessing changes in protein synthesis in the in vitro slice preparation after various treatments. Unilateral stimulation of the auditory nerve in vitro has been shown to produce similar changes in protein synthesis as those observed in vivo. Application of specific agonists and antagonists will assess the relative roles of different types of excitatory amino acid receptors and second messenger systems in transneuronal regulation of brain stem auditory system, 2) an understanding of the signals responsible for the regulation of neuronal metabolism in this system and 3) an understanding of age-related differences which may account for the age- dependence in the sensitivity of neurons to alterations of afferent activity.